With the growing awareness of the crucial role that knowledge can play in gaining competitive advantage, several issues with regard to knowledge management (KM) initiatives have challenged executives. The articulation of the relationship between an organization’s competitive strategy and its knowledge strategy is the most eminent. This chapter addresses the issue of how to align knowledge strategy with enterprise business strategy. Based on the premise that the realization of business value from KM investments requires alignment between business and knowledge strategies, the issue is addressed by developing a strategic alignment model for KM. This model, which is based on the Henderson-Venkatraman strategic alignment model, includes the external domains (opportunities/threat) and internal domains (capabilities/arrangements) of both business (B-) and knowledge (K-) strategies and the relationships between them. Furthermore, it provides alternative strategic choices. The model is used to study a KM initiative at Buckman Laboratories.