Industrial processes today operate on very large scales with the advent of modern industrial plants. Such plants sometimes operate hundreds of equipment, not to mention thousands of instruments for the measurement and control of such equipment. Efficient operation of industrial plants means higher reliability, improved safety, increased revenue, and ultimately, a satisfied consumer-base. The different plant modes like startup, continuous operation, and shutdown, present different challenges, all of which will be explored. Understandably, with such a high volume of equipment and instruments, failures are inevitable. Properly troubleshooting individual equipment failures and total plant shutdowns with a correct approach and methodology is critical for improving plant availability and reliability. A well devised maintenance strategy and periodic turnaround plan are also instrumental to that end. Furthermore, priority should be given to systematized operations and increased safety through core operations values and safety principles, and tools such as SOPs and COPs (critical operating parameters), all of which lead to more successful plants.