Before the introduction of the West Nile virus (WNV) into the United States of America (USA) in 1999, conditions in North America were ideal for an arboviral epidemic. Such factors as the large, susceptible and non-immune animal and human populations, the presence of competent vectors, increasing international travel and commerce, existing methods for rapid dissemination and an ill-prepared animal and public health infrastructure all combined to create the essential elements for a severe animal and public health crisis--the 'perfect microbial storm'. The introduction of WNV into New York City was the final factor, serving as the catalyst to initiate one of the most significant epidemics in the USA. The spread of WNV across the country resulted in very large populations of wildlife, equines and people being exposed and infected. The epidemic is still not fully understood and its character continues to change and adapt. The recent recognition of a number of non-vector modes of transmission has revealed the disease as a greater threat and more difficult to control than first thought. West Nile virus gives every indication that it will become a permanent part of the 'medical landscape' of the USA, continuing to threaten wildlife, domestic animals and humans as a now endemic disease. This paper discusses the features of this extraordinary epidemic, and emphasises the need for an integrated surveillance system, greater diagnostic capacity and improved control strategies.