Self-leadership is an increasingly current topic, not only for the sake of scholarly study and research, but not least for practical application in modern organizations. The fundamental idea of self-leadership is that employees can take on responsibility for many of the influence processes normally carried out by leaders and leadership systems. Knowledge workers is a category of employees who might be particularily in need of self-leadership, as their work is typically unstructured, cognitively taxing, and requires the right kind of mix between alone time and extensive collaboration. How to prioritize the right types of tasks, make sure to involve the right people at the right time and protect oneself from collaboration overload, generosity burnout or other types of overwork, are examples of dilemmas facing knowledge workers in their everyday working lives. Research and theoretical contributions addressing the particular concerns and needs related to knowledge workers’ self-leadership, however, are limited. In this chapter, we discuss some of the most pressing issues in relation to self-leadership by knowledge workers and present several strategies that may assist and equip them with suitable self-leadership skills and capabilities. One of the main takeouts from this review is that behavioral and structural strategies should be prioritized over cognitive ones. Moreover, senior and experienced workers should make more use of the autonomy available to them by making sure they work in a sustainable manner, as well as role-modeling such behaviors and serving as coaches and mentors for more inexperienced workers.