The assignment of performance targets, or target Safety Integrity Levels (SILs), is a critical step in the application of the Safety Instrumented System (SIS) standards, i.e., ANSI/ISA S84.0.01-1996, IEC 61508 and IEC61511. Although the SIL is a key concept in the implementation of the standards, the development and application of a method for determining the target SIL has been left to the owner/operator. The standards do, however, provide guidance on this topic and present a number of techniques that can be considered, including risk matrix, risk graph, and Layers of Protection Analysis (LOPA). Generally, the methods for SIL assignment are qualitative or semi-quantitative risk assessment methods that are based upon the judgments of an assignment team. In most cases the methods based on expert opinion and limited historical data are adequate. However, in the case of overpressure protection for reactive systems, the number and complexity of the scenarios often overwhelms these simplified approaches. There are warning signs that can aid in the identification of cases where the simplified methods may break down and provide non-conservative results. In cases such as this, a quantitative assessment should be conducted to evaluate the likelihood of SIF demands, the risk reduction supplied by the other protection layers, with the aim of determining the risk reduction required from the instrumented overpressure protection system.