Fertilization, the union of an oocyte and a sperm, is a fundamental process that restores the diploid genome and initiates embryonic development. For the sperm, fertilization is the end of a long journey, one that starts in the male testis before transitioning to the female reproductive tract’s convoluted tubule architecture. Historically, motile sperm were thought to complete this journey using luck and numbers. A different picture of sperm has emerged recently as cells that integrate complex sensory information for navigation. Chemical, physical, and thermal cues have been proposed to help guide sperm to the waiting oocyte. Molecular mechanisms are being delineated in animal models and humans, revealing common features, as well as important differences. Exposure to pheromones and nutritional signals can modulate guidance mechanisms, indirectly impacting sperm motility performance and fertility. These studies highlight the importance of sensory information and signal transduction in fertilization.