Male infertility represents about 50% of the causes of infertility in couples. The diagnosis process represents an important procedure for defining, when possible, the causes and approaching treatments (pharmacological, surgical) aimed at overcoming the problem. Several scientific studies have set out to discover early and indicative markers capable of providing information on the biological origin of infertility and increase current knowledge in the context of new potential therapeutic approaches. The prokineticin system (PROK) consists of the prokineticin 1 (PROK1) and prokineticin 2 (PROK2) proteins. Through the activation of two G-protein receptors (PROKR1 and PROKR2) regulate a wide range of biological functions, including gastrointestinal motility, circadian rhythm regulation, neurogenesis, angiogenesis, pain perception, and mood regulation. Several studies have highlighted the crucial role of the PROK system in the development and maturation of both male and female human reproductive organs. Particularly in men, the PROK system represents a new system useful to clarify some aspects of testicular pathophysiology and provide new potential hypotheses for therapeutic intervention. This narrative review aims to illustrate the state of the art regarding, in particular, the role of PROK2 in male infertility.