Misinformation poses a critical societal challenge, and current approaches have yet to produce an effective solution. We propose focusing on generalization, uncertainty, and how to leverage recent large language models, in order to create more practical tools to evaluate information veracity in contexts where perfect classification is impossible. We first demonstrate that GPT-4 can outperform prior methods in multiple settings and languages. Next, we explore generalization, revealing that GPT-4 and RoBERTa-large exhibit differences in failure modes. Third, we propose techniques to handle uncertainty that can detect impossible examples and strongly improve outcomes. We also discuss results on other language models, temperature, prompting, versioning, explainability, and web retrieval, each one providing practical insights and directions for future research. Finally, we publish the LIAR-New dataset with novel paired English and French misinformation data and Possibility labels that indicate if there is sufficient context for veracity evaluation. Overall, this research lays the groundwork for future tools that can drive real-world progress to combat misinformation.