It is apparent that, even for a highly druggable target class such as kinases, a macrocycle approach can bring important advantages with respect to potency, selectivity, and ADME properties, compared to acyclic chemotypes. Working with macrocyclic chemotypes brings with it some additional challenges with regard to synthetic effort and SAR complexity, but there are multiple successful examples to show that taking on this challenge can be repaid by markedly superior pharmacological and pharmaceutical properties. Moreover, our understanding of macrocycle structure and properties is advancing rapidly, such that application of this powerful approach to an increasing variety of drug targets can only get easier.