The diagnosis of infective endocarditis remains a challenge to physicians providing primary care. On one hand this type of infection will be rarely encountered in primary care, but on the other hand this disease carries an enormous detrimental potential. Furthermore infective endocarditis, particularly in its initial phase, often has an uncharacteristic presentation with findings and symptoms shared with many much more frequent and often harmless diseases. To confront these difficulties, which are responsible for the often delayed diagnosis of infective endocarditis, strict rules must be applied. In patients at risk for infectious endocarditis no antibiotic therapy should be instituted without prior cultures. Also, in all other patients aimless, "blind" antibiotic therapy without diagnosis of a bacterial infection should be avoided. In patients with uncharacteristic symptoms and findings compatible with the diagnosis of infective endocarditis that persist for more than 5 days, blood cultures prior to any antibiotic therapy are warranted in addition to other clinical exams and tests. The sensitivity of echocardiography in detecting infective endocarditis is frequently overestimated. Furthermore, transesophageal echocardiography in endocarditis high-risk patients requires antibiotic prophylaxis which would obscure bacteriological diagnosis. For these reasons echocardiography should not be used as first test method when considering the diagnosis of infective endocarditis.