Information is at the heart of healthcare because all stakeholders need fit-for-purpose information to make decisions. However, producing and utilizing information in the data-intensive and ever-changing health environment requires various skills. In the particular context of low- and middle-income countries, this study, consisting of a scoping review and a qualitative case study, explores the information and ICT skills of health professionals. Our review identifies challenges in several areas of health professionals’ skills, including computer skills; skills required for using the routine health information system; data security skills; and data management and analysis skills. Our South African case study, based on interviews, adds a more nuanced understanding of the different types of training needs. This assessment shows that training and education aimed at improving the ICT and information skills of health professionals have to be versatile and cater to different groups with varying needs.