Project portfolio selection (PPS) is a significant problem faced by most organizations. How to best select the many innovative ideas that a company has developed to deploy in a proper and sustained manner with a balanced allocation of its resources over multiple time periods is one of vital importance to a company's goals. This dissertation details the steps involved in deploying a more intuitive portfolio selection framework that facilitates bringing analysts and management to a consensus on ongoing company efforts and buy into final decisions. A binary integer programming selection model that constructs an efficient frontier allows the evaluation of portfolios on many different criteria and allows decision makers (DM) to bring their experience and insight to the table when making a decision is discussed. A binary fractional integer program provides additional choices by optimizing portfolios on cost-benefit ratios over multiple time periods is also presented. By combining this framework with an `elimination by aspects' model of decision making, DMs evaluate portfolios on various objectives and ensure the selection of a portfolio most in line with their goals. By presenting a modeling framework to easily model a large number of project inter-dependencies and an evolutionary algorithm that is intelligently guided in the search for attractive portfolios by a beam search heuristic, practitioners are given a ready recipe to solve big problem instances to generate attractive project portfolios for their organizations. Finally, this dissertation attempts to address the problem of risk and uncertainty in project portfolio selection. After exploring the selection of portfolios based on trade-offs between a primary benefit and a primary cost, the third important dimension of uncertainty of outcome and the risk a decision maker is willing to take on in their quest to select the best portfolio for their organization is examined.