Rabies is a zoonotic disease with the highest fatality rate of any infectious disease. The clinical features of rabies encephalopathy are highly nonspecific at the onset and clinicians from low endemic areas usually face difficulties in recognizing cases during the early stages. The need for establishing a rapid and accurate test to identify rabies during the ante-mortem period is important. However, in actual clinical practice, the latter may remain difficult for various reasons. In human rabies, positively identifying the antigen, antibody or genetic material by various diagnostic methods during the symptomatic period is affected by the unpredictable nature of viremia, levels of antibody immune response of the host, and the virulence of the infecting strain. Also, more advanced testing with greater sensitivity may not be readily available at all centers. Here we describe a case of a young male who was bitten by a rabid dog and developed progressive encephalopathy with a fatal outcome, with negative antibodies in the cerebrospinal fluid (CSF). A review of the literature on the clinical features, diagnostic tests, treatment and prevention of rabies is also presented.