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Hypocrellins, as a kind of novel phototherapeutic agents, have severaladvantages over the clinically used hematoporphyrin derivatives, including high-excited triplet state yield, high phototoxicity, low dark toxicity, and rapid metabolism. However, they exhibit little absorption in the photodynamic window (600-900 nm) and are not water soluble, which limits their application in photodynamic therapy. Sulfonated and metal-ioned hypocrellins have been designed and synthesized to improve their water solubility. Unfortunately, the water-soluble derivatives obtained exhibit lower photodynamic activity than the parent hypocrellins. Thiolated and aminated hypocrellins have also been designed and synthesizedto enlarge their photoresponse. Among them, the aminated hypocrellins possess the highest photodynamic activity. We recently have further designed and synthesized some amphiphilic aminated hypocrellin derivatives. Thus, not only the photoresponse but also the water solubility is enhanced. The experiments in vitro and in vivo on the derivatives are under way at present.