The function of the medicinal chemist in drug discovery has significantly evolved over the last 25 years, mostly due to the use of technologies like combinatorial chemistry and structure-based drug design. With a collective experience of over 50 years in medicinal chemistry, covering the last four decades, we will explore this evolving function by drawing on both our own experiences and those of others. Examining this historical viewpoint may provide valuable insights on enhancing the present drug discovery framework by enabling medicinal chemists to reclaim their creative involvement that played a significant part in previous achievements.