Decreased Leydig cell activity results in impaired testicular function, which manifests as low testosterone production, aberrant follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and reduced fertility. Leydig cells have complex interactions with other testicular cell types, including macrophages, peritubular cells, and Sertoli cells. Each of these specific interactions uniquely contributes to the overall function of the testis. Interactions with macrophages are closely linked to Leydig cell development, steroid production, and spermatogenesis. The relationship between Leydig cells and peritubular cells is equally essential, affecting Leydig cell development, spermatogenesis, and vasoconstriction. Finally, Sertoli cells play an essential role in Leydig cell development and maintenance. These various cell-cell interactions will be discussed in this review, in an effort to summarize our understanding of molecular signaling within the testis and to offer insights into the etiology of male infertility and potential therapeutic targets to improve male reproductive health.