A variety of classic and emerging soil-related bacterial and fungal pathogens cause serious human disease that frequently presents in primary care settings. Typically, the growth of these microorganisms is favored by particular soil characteristics and may involve complex life cycles including amoebae or animal hosts. Specific evolved virulence factors or the ability to grow in diverse, sometimes harsh, microenvironments may promote pathogenesis. Infection may occur by direct inoculation or ingestion, ingestion of contaminated food, or inhalation. This narrative review describes the usual presentations and environmental sources of soil-related infections. In addition to tetanus, anthrax, and botulism, soil bacteria may cause gastrointestinal, wound, skin, and respiratory tract diseases. The systemic fungi are largely acquired via inhalation from contaminated soil and near-soil environments. These fungal infections are particularly life-threatening in those with compromised immune systems. Questions regarding soil exposure should be included in the history of any patient with syndromes consistent with tetanus, botulism or anthrax, traumatic wounds, recalcitrant skin lesions, gastroenteritis, and nonresponsive, overwhelming, or chronic pneumonia. (J Am Board Fam Med 2012;25:734-744.)