Rheumatic heart disease, a neglected disease, continues to be a burden in India and other developing countries. It is a result of an autoimmune sequalae in response to group A beta hemolytic streptococcus (GAS) infection of the pharynx. Acute rheumatic fever (RF), a multisystem inflammatory disease, is followed by rheumatic heart disease (RHD) and has manifestations of joints, skin and central nervous system involvement. A review of epidemiological studies indicates unchanged GAS pharyngitis and carrier rates in India. The apparent decline in RHD rates in India as indicated by the epidemiological studies has to be taken with caution as methodological differences exist among studies. Use of echocardiography increases case detection rates of RHD in population surveys. However, the significance of echo based diagnosis of carditis needs further evaluation to establish the significance. Research in this area through prospective follow up studies will have to be undertaken by the developing countries as the interest of developed countries in the disease has waned due the declined burden in their populations. Prevention of RHD is possible through treatment of GAS pharyngitis (primary prophylaxis) and continued antibiotic treatment for number of years in patients with history of RF to prevent recurrences (secondary prophylaxis). The cost effectiveness and practicality of secondary prophylaxis is well documented. The challenge to any secondary prophylaxis program for prevention of RF in India will be the availability of benzathine penicillin G and dissipation of fears of allergic reactions to penicillin among practitioners, general public and policy makers. The authors review here the progress and challenges in epidemiology, diagnosis and primary and secondary prevention of RF and RHD.