The circle of fifths,

                                C
                         F             G      
                    Bb                     D
                    Eb                     A
                       Ab                E
                         Db           B
                            Gb  =  F#

           C# = Db,   D# = Eb,  F# = Gb,  G# = Ab,  A# = Bb
           B  = Cb,   E  = Fb,  C  = B#,  F  = E#,

One can follow the circle of fifths either clockwise or counterclockwise. The more distant the tonic note of a tonality is from another on the circle of fifths, the more harmonically distant the tonalities are; thus F# Major (Gb Major) is the most harmonically distant from C Major.

Musically speaking, the notion of harmonic distance between tonailties is directly related to the amount of musical machinations one must perform in order to modulate between them, using the rules of "classical harmony".

The above is in the context of equal temperament. If one uses perfect fifths whose tones have frequencies in the ration of 1:(3/2), the sequence of 12 fifths is:

     C G D A E B F# C# G# D# A# E# B#

     and B# is not an integral multiple of C in frequency.
     Bringing the B# down by 7 octave equivalences (dividing
     the frequency by two for each octave descent) gives
     a discepancy which is called the Pythagorean Comma.

The above is a quick and dirty explanation of a complicated fact of musical life, and does not even begin to do justice to the details. For a rather extensive and properly mathematical exposition of the problems posed and compromises involved in the concept of temperament see Pianos and Continued Fractions. This is not for the dilletante, and seems to be as good as reading [Helmholtz 1877] on the subject; in fact, it may be more accesible. Available also on the net is MTP: Algorithms for Mapping Diatonic Tunings and Temperaments