Propolis is a resinous material produced by bees from the selective collection of plant exudates that are subsequently mixed with beeswax and salivary bee secretions. Propolis has been used in folk medicine, and certainly, several studies have validated its biological properties. The chemical composition and pharmacological activities of propolis collected through North (including Central America and Caribbean) and South America have been studied in the last years, and several papers have reported differences and similarities among the analysed geographical samples. Propolis has been classified according to its aspect and plant source; however, the ecological diversity present along the Americas provides a plethora of botanical resins. Herein, we summarize and discuss most of the studies performed at present on this profitable product for apiculture, attempting to compare the bioactivity, phytochemical diversity and botanical sources of honeybee propolis produced in Americas.