The last decade has seen the emergence of immunomodulators as promising therapeutic agents in infectious diseases. A diverse array of recombinant, synthetic and natural immunomodulatory preparations for prophylaxis and treatment of various infections are available today. Some of these substances, such as granulocyte colony-stimulating factor (G-CSF), interferons, imiquimod and bacterial-derived preparations are already licensed for use in patients. Others including IL-12, various chemokines, synthetic cytosine phosphate-guanosine (CpG) oligodeoxynucleotides and glucans are being investigated extensively in clinical and preclinical studies. Immunomodulatory regimens offer an attractive approach as an adjunct modality for control of microbial diseases in the era of antibiotic resistance. Practical application of the advances in molecular biology, bioinformatics, genomic mining and high-throughput peptide synthesis should foster future discovery and development of novel immunomodulators contingent upon scientific evidence rather than dictates of discursive empiricism.