The introduction of stringent EPA 2015 regulations for locomotive / marine engines and IMO 2016 Tier III marine engines initiates the need to develop large diesel engine aftertreatment systems to drastically reduce emissions such as SOx, PM, NOx, unburned HC and CO. In essence, the aftertreatment systems must satisfy a comprehensive set of performance criteria with respect to back pressure, emission reduction efficiency, mixing, urea deposits, packaging, durability, cost and others. Given multiple development objectives, a systematic approach must be adopted with top-down structure that addresses top-level technical directions, mid-level subsystem layouts, and bottom-level component designs and implementations.This paper sets the objective to provide an overview of system development philosophy, and at the same time touch specific development scenarios as illustrations. A brief review of emission regulations is provided at the beginning, followed by definitions of system performance targets and metrics. According to these performance targets and the challenges of meeting them in multiple technical areas, focus is placed on system hardware development, component selections and layout choices including (1) PM reduction and regeneration mechanisms, options and layouts; (2) heat and reagent mixing development as urea is used for NOx reduction, and DOCs and Regeneration Units (RGU) with HC dosing are used for active regenerations; (3) pressure prediction, testing, and correlations for components and full systems; (4) a case study of NOx reduction system development and engine dynamometer validations for a marine engine. Other topics are briefly discussed such as sulfur reduction technology choices, substrate and catalyst selection which are integral to system performance.