The present article summarizes recent progress in the study of nucleoside derivatives as antiviral and immunosuppressive agents. A number of 5′-substituted 5′-deoxy nucleosides have been found to be permeable and nonincorporable antimetabolites of 5′-nucleotides. N6-isopentenyladenosine and analogs show certain promising immunosuppressive activities. Encouraged by the antibody-stimulating effect of oligonucleotides, we have developed a convenient synthesis of oligonucleotides using fully protected phosphorylated intermediates. A group of tetradeoxyribonucleotides, dApdApdApdX, was prepared for biological and physical evaluations. Nucleotide derivatives may prove valuable in the treatment of several immunological disorders.