Herbal medicine has been used in medical practice for thousands of years and recognized especially as a valuable and readily available resource for healthcare in Asian nations. India is a vast repository of medicinal plants that can be developed as a safe and economical system of medicine for the treatment of various ailments. Unfortunately, most of the traditionally used medicinal plants are yet unexplored or have not been fully examined by modern medical science. Therefore, exploring traditionally reported medicinal plants to leverage their potential for the betterment of human health is of great importance. The present review examines a promising medicinal plant genus Spilanthes. In recent years, many new compounds and activities of this plant genus have been established. The present review therefore, aims to compile up-to-date and comprehensive information of genus Spilanthes with special emphasis on phytochemical and ethnomedical uses, scientifically documented pharmacological activities and tissue culture methods for conservation.