Over the past several years, use of novel methods and novel study designs has increased exponentially in pharmaceutical R&D. These methods offer the possibility of more efficient clinical development, improved decision making and better use of precious clinical trial resources. Increased use of approaches such as Bayesian and adaptive trial designs have also highlighted the need for much closer collaboration between industry statisticians and those working at regulatory agencies. In turn this has necessitated new ways of thinking for statisticians and new mechanisms for interaction between industry and regulators. The evolving environment has been acknowledged in PDUFA VI with specific proposals aimed at increasing the quality and timeliness of interactions between industry and FDA statisticians. This talk will highlight both challenges and positive aspects of statistical interactions with regulatory agencies. Case studies will be used to highlight what has gone well learnings that can be applied to future interactions.