In this chapter we aim to promote an understanding of the complexity of healthcare as a setting for information systems and how this complexity influences the achievement of successful implementations. We define health informatics and examine its role as an enabler in the delivery of healthcare. Then we look at the knowledge commodity culture of healthcare, with the gold standard of systematic reviews and its hierarchy of evidence. We examine the different forms of quantitative and qualitative research that are most commonly found in healthcare and how they influence the requirements for health information systems. We also examine some domain-specific issues that must be considered by health information systems developers, including those around clinical decision support systems and clinical classification and coding systems. We conclude with a discussion of the challenges that must be balanced by the health systems implementer in delivering robust systems that support evidence-based healthcare processes.