Rogier van der Weyden created the famous panel of The Descent from the Cross in 1435. The work features the rich colors and portraiture representative of much Early Netherlandish art, but also focuses the viewer's attention to the scene's humanity while simultaneously emphasizing the religious nature of the image. The effective combination of these two elements would prove hugely influential to Italian Renaissance painters.

Hans Holbein the Younger is referred to with the suffix to differentiate him from his father, who was a painter of the Late Gothic school. Holbein the Younger was an innovator in the Northern Renaissance style, beginning in Germany and then moving to England to become the official painter for the court of King Henry VIII. There, he made significant advances to the art of portraiture with his paintings of the important figures of the court life in England. 

Michelangelo (1475-1564) is often considered the prototypical "Renaissance man," along with Leonardo da Vinci, thanks to his key involvement in painting, sculpture, and design. Michelangelo was one of the earliest painters to use realistic imagery, forced perspective, and an enhanced use of color. His work was key in the development of Renaissance themes like a return to classical motifs, a sense of grandeur, and the use of scientific knowledge in the arts.

Jan van Eyck was a transformative figure in European painting, as his approach to painting depended on realism and a naturalistic viewpoint. His Ghent Altarpiece, also called The Lamb of God, was a departure from Medieval standards that typically valued idealization and symbolism in religious imagery. Van Eyck, who lived from 1390 to 1441, had an outsized influence on the artistic transformations that occurred during the Renaissance.

Hans Holbein the Younger made a name for himself by painting nearly every figure associated with the court of the English king Henry VIII. In doing so, he helped pioneer a new use of perspective in his portraits. Holbein's work helped push Renaissance art to new places simply through portraits.

The Garden of Earthly Delights, painted between 1490 and 1510, is a highly idiosyncratic and complicated triptych of the Garden of Eden, earthly pleasures, and their subsequent punishment in a hell-like atmosphere. The religious overtones and multi-faceted story are features of most paintings by Hieronymus Bosch, who was an early Netherlandish painter during the Renaissance. Bosch's painting, now in the Museo del Prado in Madrid, was highly influential for its depiction of human forms, its allegorical tales, and its peculiar form of storytelling.

The painter of the Arnolfini Portrait is Jan van Eyck, who is famous for his other works in the Netherlandish style, including Portrait of a Man in a Turban.

Michelangelo Caravaggio's paintings showed a striking use of the high contrast between dark and light known as chiaroscuro, pushing the technique further than any artist had previously. He used it to give drama to many of his psychologically charged paintings of religious scenes. He also often painted boys, sometimes incorporated into these scenes and sometimes in a non-religious or Classical context.

El Greco, born Domenikos Theotopoulos (1541–1614) was a Mannerist painter and sculptor. He born in Crete and worked in Rome and Spain. His well-known work The Burial of the Count of Orgaz was commissioned in 1586 by the parish priest of Santo Tomé.

Mannerism departed from the High Renaissance style that emphasized symmetry, balance, and perfection. Instead, Mannerist artists allowed the imperfections, emotions, and disproportions of their subjects to show through, sometimes even enhancing them.