Melanization plays important roles in diverse physiological processes in insects including wound healing, tanning of the cuticle and immunity. Upon infection, pattern recognition receptors activate downstream serine protease cascades that culminate in the activation of prophenoloxidase (PPO), the rate-limiting enzyme in the process of melanogenesis. During the last two decades, diverse genetic and biochemical approaches have been adopted to characterize this process, and a wealth of information has been generated concerning the molecular events that control PPO activation. Importantly, the melanization reaction was shown to be toxic to parasites, bacteria, fungi and recently viruses. Several studies pointed also to the existence of significant crosstalk between melanization and other immune responses possibly to coordinate immune attack against invaders. Here, we provide a critical review of the role of melanization in insect immunity, highlighting the important discoveries but also the gaps that remain to be explored in future studies.