In the last decade, insertion of a therapeutic gene and nucleotide into cells termed as gene therapy has shown tremendous potential to cure life-threatening severe diseases. This therapy involves carrying the therapeutic gene to the nucleus of an affected cell through a vector. Initially viral vectors were employed for this purpose, but low production yield, limited carrying capacity, and long-term safety concerns associated with viral vectors led to the development of nonviral vectors as gene carriers. Currently, used nonviral carriers include polymers and lipids with cationic charge. Cationic polymers provide an excellent alternative for gene delivery due to their water solubility, biodegradability, ease of modification, and excellent compatibility with body systems, but challenges still persist to optimize them as ideal vectors. This chapter provides an overview of present status of cationic polymers and challenges associated with their use for gene delivery.