This paper discusses patterns of use and various functions of the frequent Thai expression mai pen rai, which can be roughly glossed as ‘never mind’. The study is based on conversational data: face-to-face and by phone. Mai pen rai is a linguistic pattern requiring appropriate knowledge for its practical use in the culture of everyday human communication. The expression mai pen rai implies a pragmatic response to culture, and acts as a psychological mechanism reflecting the influence of Buddhism (Buddhadasa Bhikkhu, 1956; Phra Khantipalo, 1993; Phra Rajakittimoli, 1997) in a relaxed Thai lifestyle. Mai pen rai demonstrates a unique communication pattern for different situations in life. It further reveals speech strategies resulting from the application of natural phonological processes, as discussed by Stampe (1979), Dressler (1989) and Fotlin and Dressler (1997). Mai pen rai can be considered as a back-channel expression (Iwasaki and Horie, 1998; Chaimanee, 1999), which is sent out as a mental response formula: a reply of thankfulness or pardon or a sign of social care, or as a politeness formula (Brown and Levinson, 1987). Since mai pen rai has multiple and effective uses, the expression highlights a practical phrase of human language in communication. Communicating with the universally underlying semantic structure – ‘never mind’ – would help all of us to live in harmony with a peaceful mind in this Global World.