Range expansion potential is an important consideration for prioritizing management actions against an invasive species. Understanding the potential for range expansion by invasive reptiles such as the Burmese python can be challenging, because the lack of knowledge on fundamental physiological and behavioral constraints initially forces reliance on modeling to predict hypothetical invasive range potential. Hypothetical predictions for Burmese python range limits in the USA have been highly divergent, from only extreme South Florida and the extreme southern Gulf edge of Texas to a broad swath over the southern third of the continental USA. Empirical observations on python thermal tolerances and behavioral abilities to cope with more temperate temperatures became evident during a cold spell in December 2009-January 2010. We review and highlight important considerations for improving invasive range estimation methodology, deciding between competing range predictions, and the importance of having, and applying, empirical data to aid in decision making.