The human immunodeficiency virus (HIV) and other viruses such as hepatitis and herpes have infected millions of people worldwide. These viruses remain global pandemics due to the continued emergence of viral resistance to current therapies. One of the most successful classes of antiviral agents is the nucleoside/nucleotide analogs. Although these drugs have been proven clinically effective, they have several drawbacks. Nucleoside analogs generally require phosphorylation by human and/or viral kinases while the bioavailability and tissue penetration of nucleotide analogs are hampered by the prevalence of a charged species at physiological pH. This work relates the investigation of boronic acids and their derivatives as potential phosphate/phosphonate isosteres with the goal of improving pharmacological properties as compared to current nucleoside phosphonates, e.g. tenofovir. The synthesis and anti-HIV activity of a library of boronic acid analogs of nucleoside monophosphates is described. Using a cellular model of HIV replication, several compounds were found to exhibit anti-HIV activity with little cytotoxicity.