Despite the immense potential of non-viral delivery system in gene therapy its application has been impaired greatly by various impediments having contrasting traits. Therefore it is an absolute necessity to develop some non-viral vectors which are endowed with special characteristics to act differently in intracellular as well as extracellular compartments to surmount these inter-conflicting hurdles. Such smart polymers should serve some specific purposes by adjusting their structural or functional traits under the influence of stimuli such as temperature, light, salt concentration or pH. Among all these stimuli-responsive polymers pH-responsive polymers have attracted major attention and great impetus has been directed towards utilizing the subtle yet significant change in pH value within the cellular compartments. This review is intended to provide a comprehensive account of the development of pH-responsive polymeric vectors based on their structural features and consequent functional attributes to achieve efficient transfection. The underlying modes of actions relating to structure and differential pH environment have also been discussed in this review.