Until 1520, the city flourished. It was the second largest population centre in the territory of the present Netherlands, after Utrecht. It was also the birthplace and home of one of the greatest painters of the northern renaissance, Hieronymus Bosch (c. 1450–1516). The city was also a center of music, with many composers, such as Jheronimus Clibano, receiving their training at the cathedrals there. Others held positions there: Matthaeus Pipelare was musical director at the Confraternity of Our Lady, and renowned Habsburg copyist and composer Pierre Alamire did much of his work at 's-Hertogenbosch.
The wars of the Reformation would soon change the course of the city. It became an independent bishopric. During the Eighty Years' War the city took the side of the Habsburg authorities. A Calvinist coup was thwarted. It was besieged several times by Prince Maurice of Orange, stadtholder of Holland, who wanted to put 's-Hertogenbosch under the rule of the rebel United Provinces. Afterwards the fortifications were greatly expanded. As the surrounding marshes made a siege of the conventional type impossible, the fortress was deemed impregnable and nicknamed the Marsh Dragon. The town was nevertheless finally conquered by Frederik Hendrik of Orange in 1629 in a typically Dutch way: he diverted the rivers Dommel and Aa, created a polder by constructing a forty kilometre dyke and then pumped out the water by mills. After a siege of three months, the city had to surrender, an enormous blow to Habsburg strategy during the Thirty Years' War. This cut the town off from the rest of the duchy. The area was treated by the Republic as an occupation zone without political liberties (see also Generality Lands). The fortifications were again expanded. In 1672, the Dutch rampjaar, the city held against the army of Louis XIV. In 1794, French revolutionary troops under command of Charles Pichegru took the city with hardly a fight: in the Batavian Republic both Catholics and Brabanders at last gained equal rights.
From 1806, the city was part of France. It was captured by the Prussians in 1814. The next year, when the United Kingdom of the Netherlands was established, it became the capital of North Brabant. Many newer and more modern fortresses were created in the vicinity of the city. Until 1878 it was forbidden to build outside the ramparts. This led to overcrowding and the highest infant mortality in the kingdom. The very conservative city government prevented industrial investment — they didn't want the number of workers to grow — and the establishment of educational institutions — students were regarded as disorderly. As a result, the relative importance of the city diminished. In World War II it was liberated from 24 to 27 October 1944 by the 53rd (Welsh) Division. After the war, plans were made to modernise the old city, by filling in the canals, slighting some ramparts and reconstructing historic neighbourhoods. Before these plans could come to effect however, the central government declared the city a protected townscape. Most historic elements have thereby been preserved.
The old city of 's-Hertogenbosch is still almost completely surrounded by continuous ramparts. On the south side, this wall still borders on an old polder, kept intact as a nature reserve, that stretches all the way to Vught. These city walls are currently undergoing renovations. Hidden below the old city is a canal network called the Binnendieze that once spanned 22 kilometres. It started out as a regular river, the Dommel, running through the city in medieval times but due to lack of space in the city, people started building their houses and roads over the river. In later times it functioned as a sewer and fell into disrepair. In recent decades, the remaining sixth of the old waterway system has been renovated, and it is possible to take several guided subterranean boat trips through it.
's-Hertogenbosch is also home to Saint John's Cathedral (Sint Jans kathedraal in Dutch) which is said to be one of the most beautiful cathedrals in The Netherlands. The Cathedral dates from circa 1220 and is best known for its (Brabantian) gothic design and the many sculptures of craftsmen that are sitting on almost every arc and rim along the outside of the cathedral. At the time of writing, the cathedral is being extensively renovated to undo the damage of many years of wear-and-tear and acid rain.
The painter Hieronymus Bosch (c. 1450 - 1516) probably remains the best known citizen of 's-Hertogenbosch.
The city has one professional football club, FC Den Bosch (first club of current Real Madrid star Ruud van Nistelrooy), and is also the home to top field hockey club HC Den Bosch, basketball team EiffelTowers Den Bosch and 2008 national rugby champion The Dukes.