The discovery and development of macrocyclic kinase inhibitors has been reviewed. Here, we focus on what we can learn from MC kinase inhibitor drugs and clinical candidates about consequences of macrocyclization that can be advantageous even for target classes where conventional druglike inhibitors are achievable. In particular, we examine the impact of macrocyclization on target binding affinity, selectivity, and pharmaceutical properties. Using examples of MC kinase inhibitor drugs and clinical candidates for which the relevant information is publicly available, we analyze how macrocyclization affected the behavior of each lead series.