We were unable to detect a virus in two thirds of the 123 dengue-like illness samples. These results could reflect true negative status, which would result from a non-viral infection, illness due to non-infectious agent, or complete immunologic clearance. Alternatively, the negative results could reflect failures in our diagnostic approaches due to imperfect sensitivity, unsatisfactory sample preparation, improper sample type, or failure to recognize highly divergent viral sequences. The presence of sequences that lack even remote similarities to known species also highlights the need for further development of de novo assembly methods for metagenomic data. Assembled data, increased depth, and enhanced sequenced comparison methods should enable more sensitive detection of divergent viruses in metagenomic samples.