**Abstract**

Topical photodynamic therapy (PDT) has been applied to treat premalignant and malignant lesions such as actinic keratosis and non-melanoma skin cancer. A limiting factor of the technique is cream permeation and studies using chemical and physical approaches to overcome it have increased over the years. This chapter is going to explore the main techniques described in the literature used to improve the cream permeation or the photosensitizer (PS) distribution concerning homogeneity. Outcomes-based on animal studies and clinical trials comparing different delivery techniques are going to be presented, highlighting the aspects of invasiveness, costs, harmfulness, and effectiveness of those methods.

**Keywords:** topical photodynamic therapy, drug delivery, skin cancer, protoporphyrin IX, precursors
