Diffuse Large B-cell Lymphoma (DLBCL) is a common type of Non-Hodgkin’s Lymphoma, marked by significant clinical and biological variability. Standard first-line treatment cures about 60% of patients, while 30-40% either do not respond or relapse. Current prognostic tools often fail to predict relapses accurately. The tumor cell’s origin accounts for some heterogeneity. Exosomes, small vesicles released by various cells, facilitate intercellular communication and are found in all bodily fluids. Analyzing exosomes for nucleic acids and proteins may provide valuable diagnostic and prognostic insights for DLBCL. We conducted literature searches using Pubmed, Cochrane, Science Direct, Wiley Online Library, and Google Scholar using the keywords “exosomes”, “HIV”, “DLBCL”, “miRNA”, and “viruses”. We found 89 articles, of which 56 met our inclusion criteria and had their significant findings assimilated into our review. Exosomes and their cargo show potential as non-invasive biomarkers for DLBCL patients. Undifferentiated naive cells exposed to exosomes containing trans-activating response element RNA are more susceptible to HIV, which can be both stimulated and inhibited by exosomes, depending on their source. Thus, targeting exosomes may be a viable approach for reducing inflammation. Our review of 56 articles indicates that analyzing exosome nucleic acids can offer prognostic insights for DLBCL patients. Exosomes are linked to drug resistance in hematopoietic malignancies and can both stimulate and inhibit HIV. Additionally, differential expression of miRNAs in DLBCL has been observed. Overall, this study highlights the potential of exosomes for diagnosis, prognosis, disease burden assessment, and understanding drug resistance.