Infective endocarditis (IE) is not the most frequent infection acquainted in intravenous drug abusers (IVDAs). On the other hand, all physicians should keep a high index of suspicion and always consider this possibility when they are dealing with an infectious process in this special population group. Since Sir William Osler, at the turn of the previous century, first described IE, there have been tremendous alterations in the very nature of this serious and possibly fatal disease. Right-sided endocarditis accounts for almost 10% of all IE episodes and has been correlated most commonly with injection of illicit drugs. However, recent reports have proposed that left-sided valves participation is seen more often now than in the past. Although, the advances in medicine and especially modern imaging techniques have expanded our capacity to identify IE, there are still some gray areas in our ability to fully comprehend right-sided IE. Hussey et al.  were the first to distinguish IE as a distinct impediment of IV narcotics abuse in 1950. Although, many reports have been published since then arguing about the aspects of this medical entity, we will try here to comprehensively review the epidemiology and predisposing factors, clinical features and complications, diagnosis, treatment and prognosis of this disease, emphasizing on those distinctive or exclusive features seen in IE patients who are injecting illicit substances.