Activin receptor-like kinase-2/Type I Activin A receptor (ALK2/ACVR1) is one of the seven members of ALKs belonging to serine/threonine (Ser/Thr) kinase family. It plays a key role in the growth and differentiation of bone, heart, brain, and other tissues. Similar to other kinases, single point mutations (gain of function) in ALK2 are involved in the pathophysiology of several types of uncontrolled cell proliferations depending on the nature of the tissue they present in. Some of the common pathological conditions related to the mutant ALK2 include diffuse intrinsic pontine glioma and fibrodysplasia ossificans progressiva. These revelations resulted in drug discovery efforts to develop therapeutic agents targeting ALK2 overexpressed tumors. Dorsomorphin was one of the first molecules reported as an ALK2 inhibitor. Later, many ALK2 inhibitors were discovered by either exploring the core structure of dorsomorphin or incorporating new heterocyclic moiety with more selectivity and potency. This chapter will provide an overview of all the ALK2 inhibitors bearing different heterocycles. We will discuss the structure-activity relationship (SAR) of ALK2 inhibitors, their modeling studies, biological activity, and SAR study.