Outbreak of interest in photodynamic therapy (PDT) in the end of last century to treat cancer and other diseases was based on promise of localized treatment, cheaper therapy and fast ablation of treated organ. One of the most attractive option of PDT is that it can evade cancer resistance to photosensitizers. PDT for cancer therapy depends on the absorption of a photosensitizer within the malignant tissue. The photosensitizing drug is then activated by light (usually from a laser) and the active drug destroys the targeted tissue. However, one must consider complex mechanism involving many factors such as diverse light and oxygen distribution in treated organs which mitigated application of this technique in the clinical practice. PDT is not simple treatment that can be done by eyeballing, this procedure require precise planning that can be done with help of complex computer programs. Computer simulation of PDT to optimize treatment depends heavily on intense calculations in all steps of this procedure and the desk top computers are finally sufficient to add physician during therapy in real time. In this mini-review challenges of photodynamic therapy are described and possible to solutions to overcome these are presented.