We are at a time where traditionally risk-adverse health care systems and their IT architecture are confronted with the deluge of data at a massive scale and tremendous variability. In many Health Systems, genomic and molecular datasets are already being generated and the amount of data is escalating quickly. In parallel, the widespread adoption of Electronic Health Records generates large amounts of data that adds a complicated layer of variability that is difficult to standardize. Lastly, there is a high-level of privacy and security needed that protect patient data as well as adhere to IT best practice guidelines. To help with this daunting challenge, the last 5 years has brought an onslaught of highly scalable and agile technologies built specifically for these large and diverse set of challenges, though not necessarily with health care in mind. This presentation will highlight the challenges faced in building and supporting petabyte scale molecular data, combined with EHR data within the constraints of a health system, both in research and clinical settings. In particular, it will outline the IT and informatics challenges of scale, standardization, security, staff and data sharing. As narrative, the presentation will give tangible examples of the work being done at the Inova Translational Medicine Institute over the past 5 years and lessons learned. The presentation will also discuss the convergence of these new technologies such as Cloud, High Performance Compute (HPC) and Massive Parallel Processing (MPP) systems built within a Hybrid Cloud and other next generation scalable IT architectures.