The management of a portfolio of Business Models can help high technology SMEs make strategic decisions. This chapter highlights the use of methodology based on a portfolio of Business Models to ensure the medium term development of a company and its long term development, using a balanced grid of Business Models. The case used to illustrate the approach shows how PX’Therapeutics, a French biotechnology company, built its strategy and translated it into its portfolio of Business Models. This grid positions the level of promise and the level of risk for each Business Model. The latter, represented graphically, enable a manager to show the balance of the portfolio.