This paper reviews existing literature on motivation and knowledge work, and empirical studies in different environments and industries on knowledge work and worker. It also surveys 150 Nigerian knowledge workers with diverse characteristics. It holds that the optimal strategies for managing and motivating knowledge workers are job redesign to increase the intrinsic motivational value of the jobs; competitive financial rewards, empowerment and flexibility, equity, fairness, respect and regard; a conducive environment that would enable them to bloom and exercise their intellect unhindered, including making mistakes and learning from it in a connected organisation; leadership practices that are responsive to their peculiarities; a leader that is a coach, mentor and enabler and who should be able to convincingly explain why a knowledge worker should agree to be managed by him, and an organizational structure that is devoid of undue bureaucracy and protocols and frees them for optimal performance.