We have been developing methods to target drugs specifically to pathologic cells, thereby avoiding collateral toxicity to healthy cells. In the case of cancer, we have exploited up-regulation of the folate receptor on cancers of the ovary, lung, kidney, endometrium and breast to target imaging and therapeutic agents to these cancers. Clinical trials of six folate-linked drugs demonstrate that the ligand-targeting strategy holds promise for increasing drug potency while reducing unwanted toxicity. Data on treatment of tumor-bearing mice, dogs, and humans will be presented. We have also developed a targeting ligand that selectively delivers attached drugs to PSMA on prostate cancer cells. Imaging and therapeutic studies suggest that this targeting ligand can not only improve the diagnosis of prostate cancer, but also enhance treatment of the disease. Recent pre-clinical and clinical data on this targeting ligand confirm this anticipation. Additional cancer-specific ligands that target malignancies of the bladder, pancreas, stomach, brain, liver, colon, skin and esophagus are also under investigation. Moreover, use of these ligands to “light up” cancer tissues with tumor-targeted fluorescent dyes during surgeries are being developed and videos of recent surgeries of ovarian and lung cancers will be presented. Finally, ligand-targeted imaging and therapeutic agents for a number of autoimmune and inflammatory diseases (e.g. rheumatoid arthritis, Crohn’s disease, psoriasis, atherosclerosis, osteoarthritis, etc.) will also be described.