The problem of poor regulatory compliance has been widely reported across private health providers in developing countries. Less known are the underlying reasons for poor compliance, especially with regards to the roles played by front-line regulatory staff, and the regulatory institution as a whole. We designed a qualitative study to address this gap, with the study questions and tools drawing on a conceptual framework informed by theoretical literature on regulation. Data were collected from specialized drug shops (SDSs) in two rural districts in Western Kenya in 2011 through eight focus group discussions, and from regulatory staff from organizations governing the pharmaceutical sector through a total of 24 in-depth interviews. We found that relationships between front-line regulators and SDS operators were a strong influence on regulatory behaviour, often resulting in non-compliance and perverse outcomes such as corruption. It emerged that separate regulatory streams operated in urban and rural locations, based mainly on differing relationships between the front-line regulators and SDS operators, and on broader factors such as the competition environment and community expectations. Effective incentive structures for regulatory staff were either absent, or poorly linked to performance in regulatory organizations, resulting in divergences between the purposes of the regulatory organization and activities of front-line staff. Given the rural-urban differences in the practice environment, the introduction of lower retail practice requirements for rural SDSs could be considered. This would allow illegally operated shops to be brought within the regulatory framework, facilitating good quality provision of essential commodities to marginalized areas, without lowering the practice requirements for the better complying urban SDSs. In addition, regulatory organizations need to devise incentives that better link the level of effort to rewards such as professional advancement of regulatory staff.