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The locus coeruleus (LC) is a small nucleus that is located in the pontine tegmentum, and derives its name (literally meaning ‘blue spot’) from its color, which is a result of neuromelanin deposits within its cell bodies. The LC projects widely to the forebrain (Figure 1) where it releases norepinephrine (NE; also referred to as noradrenaline)(Aston-Jones et al., 1984; Berridge and Waterhouse, 2003). Catecholamines such as NE do not have a unitary effect on their target neurons, but instead influence the function of other neurotransmitters, a process that is known known as neuromodulation. By virtue of the LC’s wide projection profile and the neuromodulatory properties of NE, the LC-NE system profoundly influences neural firing characteristics and associated cognitive processes (Berridge and Waterhouse, 2003; Aston-Jones and Cohen, 2005; Bouret and Sara, 2005; Yu and Dayan, 2005). In this introductory chapter, an overview of current findings and accounts pertaining to the LC-NE system and its relationship with ‘brain state’(defined further below) and cognition is presented, followed by a summary of the chapters of this dissertation.