This chapter indicates the advanced issues of health informatics; the advanced issues of Clinical Decision Support System (CDSS); CDSS and Computerized Physician Order Entry (CPOE); the false positive alerts in CDSS; and CDSS and biomedical engineering. Health informatics and CDSS are the advanced health care technologies with the support of many technological fields. Health informatics and CDSS apply various computerized devices to provide enhanced health-related outcomes in terms of problem solving, analytical thinking, and decision making. Health informatics and CDSS help clinicians and health care providers to make complex information useful in supporting clinical decisions, thus delivering the best standard of care for each patient. The chapter argues that utilizing health informatics and CDSS has the potential to increase health outcomes and reach strategic goals in global health care.