Fresh produce is an important part of a healthy diet and is consumed in greater quantity in the United States than ever before. Consumption of cantaloupe has recently been associated with several large outbreaks of infections in North America, highlighting the need for a better understanding of practices and processes that may contribute to contamination. We reviewed all cantaloupe-associated outbreaks that were reported to the Centers for Disease Control and Prevention (CDC) and published in the literature. Twenty-three outbreaks occurred between 1984 and 2002; 1434 people became ill, 42 were hospitalized, and two died in these outbreaks. Aetiological agents in the outbreaks included five serotypes of Salmonella enterica, Campylobacter jejuni, Escherichia coli O157:H7, and norovirus. We reviewed processes contributing to cantaloupe contamination, conditions affecting survival and growth of bacterial pathogens on melons, and potential methods for sanitization. For maximum safety, industry, federal, and international partners must collaborate to ensure that appropriate interventions are in place to minimize the risk of contamination and prevent the growth of pathogens during cantaloupe production, processing, storage, and preparation.