2-Aminoimidazole skeleton represents a unique building block which is often used in the design of modulators of different targets and small molecule drugs. Alkaloids isolated from marine sponges are known to be one of the most common sources of the 2-aminoimidazole compounds and from a medicinal chemistry perspective, the marine alkaloids' fascinating structures as well as their broad spectrum of pharmacological activity make them promising lead compounds for various druggable targets. This review will focus on the presentation of biologically evaluated 2-aminoimidazole compounds showing a variety of pharmacological properties and their structure-activity relationship. The importance of 2-aminoimidazoles as bioisosteres of guanidine, acylguanidine, benzamidine and triazole groups will be highlighted.