Fifty years ago many of the key physiological processes defining plant development and growth had to some extent been defined. However, there was little research directed at understanding how these processes function in crop plants and how they might be changed to influence crop growth and yield under field conditions. In the past 50 years, there was considerable research to understand, identify, and incorporate superior metabolic and physiological activity into crop species. Important advances were made in documenting the critical physiological traits that were associated with yield increases achieved in empirical breeding programs. Unfortunately, the expectation that selection and breeding for specific physiological improvements could lead to yield increase was rarely successful. Genetic variation was found for many physiological traits and often the traits were shown to be heritable. The difficulty was that specific traits were found either to be irrelevant in the cropping environment or to have little impact on yield in tracking traits from the molecular level through to the production of grain. However, there have been cases of success using the physiological approach to produce varieties with increased yields under conditions of environmental stress. Important attributes of these successful projects included attention to phenotyping traits under field conditions and to assessing the potential benefit of the trait in a range of environments. Also, it was critical that these projects were able to sustain long-term commitments both by scientists in multi-disciplinary groups and by funding entities. The successful physiological projects in the past may well indicate the approach and commitment needed in the future to successfully exploit new genetic diversity in specific biochemical and physiological alterations available in transformed plants.