Connecting a Python application to a MySQL database can be challenging due to various connection drivers and operating system compatibility issues. This article provides four methods to connect to a MySQL database using PlanetScale, a serverless database platform for MySQL, including mysqlclient, mysql-connector-python, PyMySQL, and aiomysql. The process involves setting up a free database on PlanetScale, generating connection credentials, and installing the required Python packages. Each method has similar syntax due to the Python database API specification, and examples are provided to demonstrate how to connect to MySQL using each driver, including handling SSL encryption for secure connections.