Handling large files in applications can pose significant challenges, particularly when memory usage is a concern. A common pitfall is attempting to load an entire file into memory, which can lead to crashes on systems with limited resources. This lesson highlights the importance of designing code that can efficiently process files without exceeding memory limits. Key strategies discussed include using the `os.open` function to read files in manageable chunks rather than all at once, implementing a loop to read bytes iteratively, and employing subslices to handle only the bytes that were recently read. Additionally, the optimal size of the buffer is addressed, emphasizing the use of powers of two and multiples of the operating system's block size for more efficient file handling. This approach ensures that applications are robust and capable of running on a variety of devices, from powerful machines to resource-constrained environments.