Selecting the most efficient synthetic processes remains a complex challenge, as it often requires balancing high reaction yields with sustainability considerations. In this context, bio-click chemistry has emerged as a powerful interdisciplinary approach that combines the efficiency of click chemistry with the inherent sustainability of enzymatic processes. This specialized category of chemoenzymatic reactions holds significant promise for the development of sustainable methods and the synthesis of bioactive compounds. This chapter reviews the most relevant bio-click chemistry reactions reported in recent years, with a particular focus on their applications in medicinal chemistry.