As HIV infection may be non-symptomatic for many years, many HIV-infected individuals are not aware of their infection. At a certain point in time non-specific symptoms may occur for which patients are likely be referred to internal medicine outpatient clinics. In the absence of systematic screening for HIV and in particular in patients who do not have classical risk factors for HIV, the diagnosis of HIV infection may easily be overlooked. In this manuscript it is illustrated that this diagnostic and therapeutic delay can lead to increased morbidity and mortality. Moreover, undiagnosed individuals are on average more likely to transmit HIV than diagnosed individuals. It is important for public health to identify people harbouring HIV infection, as this is expected to reduce the number of new infections. HIV infection should be considered a possible cause of unexplained symptoms in an early stage of the diagnostic process, in particular in patients with symptoms such as unexplained fever, lymphadenopathy or weight loss or in the presence of conditions suggestive of possible immune deficiency, regardless of the absence of risk factors.