The fifteen articles in this special section focus on data science used in smart healthcare applications. A shift toward a data-driven socio-economic health model is occurring. This is the result of the increased volume, velocity and variety of data collected from the public and private sector in healthcare, and biology in general. In the past five-years, there has been an impressive development of computational intelligence and informatics methods for application to health and biomedical science. However, the effective use of data to address the scale and scope of human health problems has yet to realize its full potential. The barriers limiting the impact of practical application of standard data mining and machine learning methods have been inherent to the characteristics of health data. Besides the volume of the data (‘big data’), these are challenging due to their heterogeneity, complexity, variability and dynamic nature. Finally, data management and interpretability of the results have been limited by practical challenges in implementing new and also existing standards across the different health providers and research institutions. The scope of this Special issue is to discuss some of these challenges and opportunities in health and biological data science, with particular focus on the infrastructure, software, methods and algorithms needed to analyze large datasets in biological and clinical research.