This chapter describes strategies and methods for speciation investigations using mainly hyphenated techniques of liquid chromatography (LC) with element-specific detection. Complete speciation schemes are discussed, starting with the sources of error and problem solutions for sampling and ending with more dimensional, orthogonally chosen coupled-speciation techniques for quality controlled results. The focus in each section is directed to the specific problems being faced with respect to speciation analysis—species stability during sample storage and processing, the choice of the most suitable speciation approaches (direct methods or hyphenated techniques), species separation techniques ranging from ultrafiltration to various forms of LC, and capillary electrophoresis, discussing their advantageous as well as their (undesired) potential of changing species. Further, problems in interfacing to element-specific detectors, mainly plasma-based detectors such as inductively coupled plasma optical emission spectrometry (ICP OES) and inductively coupled plasma mass spectrometry (ICP MS), are reported. The chapter concludes with aspects of quality control, including sources of errors and strategies to overcome such problems, such as orthogonal speciation concepts.