Factors affecting short-term and long-term performance of plastics in durable applications can be divided in three main groups. The first one characterizes the basic material that includes chemical makeup, molecular architecture, molecular weight distribution, additives, etc. The second group represents material fabrication and parts manufacturing conditions. The third one consists of characteristics of parts assembling or installation procedure, and service conditions that include load level, loading rate, temperature, chemically aggressive environment, etc. Successful design of plastic components for intended application requires an understanding of the role of the above factors combined with economic consideration that takes into account the cost of fabrication as well as the price of failure. Determination of what constitute the success and failure is not universal; it depends on point of view, engineering, economic, esthetical or political one. From an engineering viewpoint, the success means retention for a specified duration of time of the desired properties such as insulation, stiffness, strength, toughness, etc. Material characterization and ranking with respect to these properties provide a basis for rational designing for specific applications. In addition, observations and characterizations of field failure modes and micro-mechanisms and incorporation of such knowledge into design lead to a significant reduction of the chances of premature failure. There are industrial standards and regulations develop to assist in selection of testing protocols for desired properties, as well as the methods of durability and lifetime prediction for engineering thermoplastics. A number of illustrative examples of successful design of molecular architecture, material and structure fabrication process, and methodology of material durability and structural reliability assessment will be discussed. Examples of the design and accelerated testing errors will be also presented.