Chief information officers (CIOs) have a unique role in today’s dynamic and competitive business environment. They must deal with the impacts of external environmental changes, changing internal customer needs, and rapidly changing technology. New models for the organization suggest that CIOs should create and manage an enterprise IT organization that is more flexible to manage uncertainty. During a two-year ethnographic study, the lead researcher observed and interviewed CIOs to determine current CIO practices for managing uncertainty. Findings from the study also include CIO recommendations on how enterprise IT organizational flexibility can help to balance the need for lean and effective operations with the need for creative and innovative ones. This paper reports on one aspect of the study: CIO leadership. The findings suggest that a CIO’s ability to be flexible is critical if the enterprise IT organization is to deal with and manage uncertainty. Flexible CIOs, it was found, respond to three types of environmental uncertainty (global, enterprise, and IT), and do so by three means of flexibility response – anticipation, agility, and adaptation. Flexible CIOs who are proactive to unexpected change manage uncertainty as if it were an opportunity.