This paper aims to advance a simultaneously conceptual and practical framework that links human resource management (HRM) and KM. A literature-based preliminary framework assumes that a number of critical KM characteristics and KM-related human resource (HR) practices impact on KM effectiveness. Qualitative methods are used for data collection and analysis. Three knowledge-intensive Spanish business units of multinational companies are the target case-study settings. Systematic patterns are found regarding the impact of critical KM characteristics and KM-related HR practices on KM effectiveness. The lack of a longitudinal study demands caution in the results interpretation. Also, similar studies in cultural contexts other than Spain could produce differing results. Moreover, further qualitative methods would be helpful for explanatory framework refinement, whereas quantitative surveys would test propositions, thus assessing the statistical generalisability of the results. KM-enhancing recommendations for practitioners are discussed. Special emphasis is placed on the great complexity that social and cultural issues pose on KM, and on senior managers' key actions aimed at involving the HR function more in KM strategy development. This paper helps to advance a better understanding of the causes of KM success or failure, useful both to academics seeking theory building and to practitioners interested in insightful advice