Native American populations have been using herbs for millennia to treat ailments and diseases. Male sexual and reproductive health has also been addressed by traditional American herbal medicine using mainly native plants. As a megadiverse zone, the materia prima of this therapeutic approach is vast. In recent years, scientific methods have been used to test the validity of traditional knowledge and to find novel pharmacological agents to treat the ever-growing demand for andrological therapies. This chapter aims to gather evidence of American herbs with attributed effects in andrological issues. Species from North America, Central America, and the Caribbean and South America are reviewed. The majority of studies have been done with in vitro and in vivo models and lack human trials to confirm reliably their properties but enough evidence to justify further research is provided, especially in species such as Lepidium meyenii (Maca), Serenoa repens, and Cucurbita pepo.